OBJECTIVE: To determine the frequency of subclinical vitamin D deficiency in an ambulatory care setting.
METHODS: This was an observational study which measured 25 vitamin D levels in medical clinic patients. Patients with chronic renal failure, known osteomalacia and rickets were excluded. A total of 119 patients were evaluated. They were divided in three diagnostic categories based on their serum 25 vitamin D levels. Those with levels below 8 ng/ml were categorized to have severe deficiency, levels between 8 - 20 ng/ml as moderate deficiency and levels of 21-35 mg/ml as mild deficiency.
RESULTS: Of 119 patients, 92% had vitamin D deficiency. Their mean age was 44.3 +/- 18.3 years, with female to male ratio of 5:1. Sixty two percent (62%) had severe, 24% moderate and 8% had mild deficiency. Nearly half of all these patients (including those with severe deficiency) were asymptomatic. Whereas a low serum calcium, elevated phosphate and elevated alkaline phosphatase were reflective of severe deficiency. It was only an elevated iPTH that correlated with mild to moderate deficiency.
CONCLUSION: Subclinical vitamin D deficiency is extensive in the adult ambulatory care patients. Serum calcium, phosphate and alkaline phosphatase are poor markers of moderate to mild deficiency. A serum 25 vitamin D level and an iPTH are better biofunctional markers of this deficiency

Habib, Aysha

Haque, Naeemul

Jabbar, Abdul

Zuberi, Lubna M

eCommons@AKU

eCommons@AKUSection of Diabetes, Endocrinology andMetabolism Department of MedicineSeptember 2008Vitamin D Deficiency in ambulatory patientsLubna M ZuberiAga Khan UniversityAysha HabibAga Khan UniversityNaeemul HaqueAga Khan UniversityAbdul JabbarAga Khan UniversityFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_diabet_endocrinol_metabPart of the Endocrine System Diseases Commons, and the Endocrinology, Diabetes, andMetabolism CommonsRecommended CitationZuberi, L., Habib, A., Haque, N., Jabbar, A. (2008). Vitamin D Deficiency in ambulatory patients. Journal of the Pakistan MedicalAssociation, 58(9), 482-4.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_diabet_endocrinol_metab/9IntroductionThe nutritional importance of vitamin D inmaintaining bone health in undebatable as is the developmentof rickets and osteomalacia caused by its deficiency. Over thepast decade, the importance of 25- hydroxyvitamin D inmaintaining the health and the function of the immune,reproductive, muscular, skeletal, and integumentary systemof people of all ages and races have come to the forefront1.Evidence supported strong association between vitamin Dstatus and risk of chronic disease that can now be linked tovitamin D intake and reduced sun exposure2.Surprisingly several recent studies have identified ahigh prevalence  of vitamin D deficiency and insufficiency inotherwise healthy adults and children living in North Americaand Europe. There are reports of extensive vitamin Ddeficiency in nursing home patients3, seasonal variation invitamin D levels related to sun exposure4 and the benefits thatpost menopausal women get from its replacement5.Osteomalacia in Pakistani women has been well documentedin literature6,7, but scant evidence exists regarding prevalenceof vitamin D status in asymptomatic patient population.The aim of this study was to determine the frequency ofvitamin D deficiency in an ambulatory care setting in Pakistan.MethodsA review of cases presenting to the endocrine andmedicine clinics at Aga Khan University Hospital, Karachiwas done. A total of 224 patients referred for measurementof vitamin D levels were enrolled, between May 2002 andDecember 2004. Patients under the age of 16 years, thosewith chronic renal failure, primary hyperparathyroidism,those with established diagnosis of rickets andosteomalacia, those taking phenytoin or glucocorticoidswere excluded from the final analysis. Majority of thesepatients were being followed at the endocrine clinic fordiabetes, obesity, hypertension or hyperlipidemia. Otherswere seen in general medicine clinic for variousnonspecific symptoms. Recorded variables includedbiochemical measurements of serum calcium, phosphorus,albumin, alkaline phosphate and intact parathyroidhormone. The measurement of 25 hydroxyvitamin D wasperformed in the hospital laboratory with aradioimmunoassay kit from DiaSorinR, using I125 forquantitative determination.For the purpose of this study, patients weredivided into three diagnostic categories based on theirserum 25 vitamin D levels. Those with levels below 8ng/ml were categorized to have severe deficiency, levelsbetween 8 - 20 ng/ml as moderate deficiency and levelsof 21 - 35 mg/ml as mild deficiency.The Statistical Package for Social Sciences SPSS(Release 13.5, standard version) was used for data analysis.Descriptive analysis was done for demographic and clinicalvariables. Results are expressed as mean + standarddeviation for quantitative variables and number482 J Pak Med AssocOriginal ArticleVitamin D Deficiency in Ambulatory patientsLubna M. Zuberi1, Aysha Habib2, Naeemul Haque3, Abdul Jabbar4Department of Medicine1,3,4, Department of Chemical Pathology2, Aga Khan University Hospital, Karachi.AbstractObjective: To determine the frequency of subclinical vitamin D deficiency in an ambulatory care setting.Methods: This was an observational study which measured 25 vitamin D levels in medical clinic patients.Patients with chronic renal failure, known osteomalacia and rickets were excluded. A total of 119 patients wereevaluated. They were divided in three diagnostic categories based on their serum 25 vitamin D levels. Those withlevels below 8 ng/ml were categorized to have severe deficiency, levels between 8 - 20 ng/ml as moderatedeficiency and levels of 21 - 35 mg/ml as mild deficiency.Results: Of 119 patients, 92% had vitamin D deficiency. Their mean age was 44.3 + 18.3 years, with female tomale ratio of 5:1.Sixty two percent (62%) had severe, 24% moderate and 8% had mild deficiency. Nearly half ofall these patients (including those with severe deficiency) were asymptomatic. Whereas a low serum calcium,elevated phosphate and elevated alkaline phosphatase were reflective of severe deficiency. It was only anelevated iPTH that correlated with mild to moderate deficiency. Conclusion: Subclinical vitamin D deficiency is extensive in the adult ambulatory care patients. Serum calcium,phosphate and alkaline phosphatase are poor markers of moderate to mild deficiency. A serum 25 vitamin D leveland an iPTH are better biofunctional markers of this deficiency (JPMA 58:482;2008).(percentage) are reported for qualitative variables. Chisquare test or Fisher exact test was used to assess thedifferences in proportion, p-value less than 0.05 wasconsidered statistically significant. ResultsA total of 119 patients were selected for finalanalysis. Their mean age was 44.3 ± 18.32 years,majority were females, in the ratio of 5:1. The mostcommon reason for requesting vitamin D level includedgeneralized myalgias and bone pains (51%). Otherreasons included presence of proximal myopathy onphysical exam (9%), underlying osteoporosis (9%) orfractures (6%). Symptom complex of chronic fatigue, legpains and low grade fever were present in some patients.Twenty one percent (21 %) of the group had diabetes and27% had hypertension. The mean serum albumin was 3.5± 1.9 mg/dl, and the mean haemoglobin level was 11.36± 1.8 gm/dl.Ninety five percent of the patients had deficientvitamin D levels. Of the total, 62% had severe, 24% hadmoderate and 8% had mild deficiency. Table shows thedemographic and laboratory characteristics of thesethree groups. Of all those with low vitamin D levels,more women had severe deficiency (68% in women  and37% in men), whereas moderate to severe deficiencywas equally prevalent in both sexes. Surprisingly 40 %of the patients did not have symptoms suggestive of orattributable to hypovitaminosis D. The three groupswere matched in terms of Body Mass Index (BMI).Symptoms of bone pains were not predictive ofunderlying D deficiency, and did not indicate theseverity of this deficiency. As expected those withsevere deficiency were more likely to have lower serumcalcium (P < 0.001), lower serum phosphate (P < 0.004)and higher parathyroid hormone levels (P < 0.01).Serum alkaline phosphate levels did not show statisticaldifference between the three groups. Of note is that inthose with moderate and mild deficiency serumcalcium, phosphate and alkaline phosphate remainednormal. The only biochemical abnormality relating to Ddeficiency in these two groups was an elevatedparathyroid hormone level.Presence of other comorbid conditions such asdiabetes, hypertension, coronary artery disease and obesitydid not influence severity of D deficiency.DiscussionA widespread deficiency of vitamin D levels inambulatory general medicine clinic patients was observedin this study. What was more of a surprise was their meanage. As a cohort this group was much younger than anypreviously reported in populations at risk of vitamin Ddeficiency. Vol. 58, No. 9, September 2008 483Table: Demographic, clinical and laboratory features of patients with Vitamin D deficiency.Vitamin D LevelFeatures < 8 IU 9 - 20 IU > 21 IU P-value(n=74) (n=29) (n=15)Age (in years) 41.1 ± 18.9 47.5 ± 14.1 53.3 ± 20.6 0.041GenderMale 7 (37%) 7 (37%) 5 (26%) 0.035Female 67 (68%) 22 (22%) 10 (10%)Bone painsYes 39 (65%) 12 (20%) 9 (15%) 0.439No 35 (60%) 17 (29%) 6 (11%)Body mass index (kg/m2) 25.3 ± 7.8 29.0 ± 6.3 27.5 ± 7.1 0.079Serum Calcium 8.0 ± 1.5 9.1 ± 0.7 9.8 ± 1.7 < 0.001Serum Phosphate 2.9 ± 1.2 3.9 ± 1.2 3.5 ± 1.2 0.004Alkaline Phosphate 272.2 ± 338.6 122.9 ± 98.0 85.5 ± 63.7 0.070Parathyroid Homon 317.7 ± 280.1 99.5 ± 88.4 95.9 ± 151.4 0.010Results are presented as mean ± standard deviation, and number (percentages).There are sporadic reports of vitamin D deficiencyand subclinical osteomalacia in pregnant and lactatingwomen from Pakistan. The first report of the presence of"occult osteomalacia" was published in Lancet in 19768.This showed that 12.6% of healthy and 33% of pregnantwomen attending a government hospital’s out patient clinichad biochemical abnormalities in their serum calcium,phosphorus and alkaline phosphatase levels, which wereconsistent with osteomalacia. Low vitamin D levels havebeen reported by M Atiq et al in 48% of healthy Pakistaninursing mothers8. Their group also showed that higherprevalence was found in mothers belonging to the uppersocioeconomic class. Clearly these reports are in high riskpopulations, such as nursing mothers and patients belongingto a lower socioeconomic background, unlike our studypopulation.More recently population based studies fromNorway, in immigrant Pakistanis have shown that seriousvitamin D deficiency and secondary hyperparathyroidismis four times as prevalent in Pakistani women thanNorwegian women. Similarly Pakistani men had fivetimes as much vitamin D deficiency and secondaryhyperaparathyroidism, as Norwegian men10. In anotherreport, in five different immigrant groups living in Oslo,Pakistani women had the highest prevalence of vitamin Ddeficiency11.The reasons behind such a high prevalence ofvitamin D deficiency in our population are unclear, but mostlikely multiple. It could be ascribed to the lack offortification of vitamin D in our diets or consumption of lowvitamin D containing foods. An alteration in the vitamin Dmetabolism has been postulated after finding in increased24 hydroxylase activity in skin fibroblasts of SouthAsians12. Environmental agents such as betel nut chewinghas been shown to be an independent determinant ofincreased 24 hydroxylase expression and of decreasedserum calcitriol levels13.A lot has been written in the literature with regardsto vitamin D deficiency in the elderly, the institutionalizedand the nursing home patients, and recently in hospitalizedpatients14,15. The present study showed the severity of thisproblem is in the outpatient setting. Though subclinical innearly half of the patients, levels below 35 ug/dl haveclearly been shown to decrease calcium absorption,stimulate iPTH production and lower bone mineraldensity16. Recent investigations by Haeney et al have shownthat iPTH can serve as a functional biomarker of vitamin Ddeficiency17.Vitamin D deficiency is prevalent in the outpatientclinic setting. In those suspected to have vitamin Ddeficiency serum 25 hydroxyvitamin D and Parathyroidhormone levels should be requested, as serum calcium,phosphorous and alkaline phosphate levels remain normalin those with mild to moderate deficiency.References1. Whiting SJ, Calvo MS. Dietary recommendations for: a critical need forfunctional points to establish an estimated average requirement. J Nutr 2005;135(2):304-3092. Heaney RP. Long latency deficiency disease: insights from calcium andvitamin D. Am J Clin Nutr 2003; 78:912-9193. Mosekilde L. Vitamin d and the elderly. Clin endocrinology 2005; 62:265-2814. Levis L, Gomez A, Jimenez C, et al. Vitamin D deficiency and seasonalvariation in an adult south Florida population. J Clin Endocr Metab 2005;90(3)1557-1562.5. Cranney A, Guyatt G, Griffith L, et al. Summary of meta-analysis of therapiesfor postmenopausal osteoporosis. Endocrine Reviews 2002; 23(4):570-578.6. Herm FB, Killgus H, Stewart AG. Osteomalacia in Hazara District, Pakistan.Trop Doct 2005; 35(1):8-10.7. Shahibzada AS, Khan MS, Javed M. Presentation of osteomalacia inKohistani women. J Ayub Med Coll 2004; 16(3):63-65.8. Rab SM. Occult osteomalacia amongst health and pregnant women inPakistan. Lancet 1976; 2(7997):1211-1213.9. Atiq M, Suria A, Nizami SQ, Ahmed I. Maternal vitamin d deficiency inPakistan. Acta Obstet Gynecol Scand 1998; 77(10):970-973.10. Meyer HE, Falch JA, Sogaard AJ, et al. Vitamin D deficiency and secondaryhyperparathyroidism and the association with bone mineral density in personswith Pakistani and Norwegian background living in Oslo, Norway, The OsloHealth Study. Bone 2004; 35(2):412-417.11. Holvik K, Meyer HE, Haug E, et al. prevalence and predictors of vitamin Ddeficiency in five immigrant groups living in Oslo, Norway: the Osloimmigrant Health Study. Eur J Clin Nutr 2005; 59(1): 57-63.12. Awumey EM, Mitra DA, Holis BW, et al. Vitamin D metabolism is altered inAsian Indians in the southern United States: a clinical research center study.J Clin Endocrinol Metab 1998; 83(1):169-173.13. Ogunkolade WB, Boucher BJ, Bustin SA, et al. Vitamin D metabolism inperipheral blood mononuclear cells is influenced by chewing betel nut(areca catechu) and vitamin D status. J Clin Endocrinol Metab 2006;91(7):2612-2617.14. Thomas MK, Lloyd-Jones DM, Thadani RI et al. Hypovitaminosis D inmedical inpatients. NEJM 1998; 338 (12): 778-783.15. Lyman D. Undiagnosed vitamin D deficiency in the hospitalized patient. AmFam Physician 2005; 71(2):299-304.16. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in theelderly: consequences for bone loss and fractures and therapeuticimplications. Endocr Reviews 2001; 22(4):477-501.17. Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within thereference range for serum 25-Hydroxyvitamin D, J Am Coll Nutr, 2003,22:142-146.484 J Pak Med Assoc

Vitamin D Deficiency in ambulatory patients

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Vitamin D Deficiency in ambulatory patients

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